JAK2基因於本態性血小板血症之研究

The study of JAK2 gene in essential thrombocythemia

蕭惠樺(Hui-Hua Hsiao)

指導教授 ： 林勝豐

高雄醫學大學/醫學院/醫學研究所/博士(2011年)

https://doi.org/10.6832/KMU.2011.00084

摘要

本態性血小板血症（essential thrombocythemia，簡稱ET）是骨髓增生性腫瘤 (myeloproliferative neoplasms，簡稱MPNs) 的一種，臨床上常常會有血小板數目過高，導致病人有血栓症或流血不止的情形發生，至今其真正的致病機轉仍未完全明瞭。近幾年來發現JAK2 V617F突變和本態性血小板血症有相當大的關係。因此我們收集本態性血小板血症之病人，進行JAK2 V617F的突變分析，並研究附近的特定單一核苷酸多型性SNP和JAK2的負向調控因子，以增加其致病機轉的了解。
我們的研究顯示於61位本態性血小板血症病患中，有34位（55.7%）有 JAK2 V617F變異。而這樣的變異和病人的白血球升高,血色素升高及血栓症的發生有相關 (p<0.05)。我們並發現特殊的SNP 和JAK2 V617F的出現有相當的關係 (p<0.05) 我們再利用allelic-specific PCR 的方法，確定rs10974944上的G-allele和JAK2 V617F是在同一條染色體上。而定量PCR也發現，負向調控因子SOCS及PIAS的表現於本態性血小板血症和正常人之間有差異(p<0.05)。
我們對於JAK2的研究，除了確定我們病人有55.7%帶有JAK2 V617F的變異於之外，也發現這種變異也和病人的臨床症狀相關。我們也確定了病人的特殊基因型式和JAK2 V617F的出現有關聯性，並且是存在於同一條染色體之上。暗示了這些特殊的基因型，可能提供了某些基因突變的誘因造成生長的優勢，以利本態性血小板血症之發展。而SOCS及PIAS等負向回饋抑制因子也參與了疾病的機轉。這些研究有助於了解本態性血小板血症的致病原因及疾病機轉。

關鍵字

JAK2 ； 本態性血小板血症 ； 單一核苷酸多型性

並列摘要

Essential thrombocythemia (ET) is one of the myeloid proliferative neoplasms with marked thrombocytosis and complications of thrombosis and/or bleeding events. The real pathomechanism of ET is still unknown. Recently, a novel finding of Janus kinase 2 (JAK2) mutation over V617F is noted on ET patients and further investigations also noted that the mutation is associated with special SNPs (single nucleotide polymorphism). Therefore, we enrolled our ET patients to study the JAK2 V617F status and the relationship with clinical presentations. We also investigated the relationship between JAK2 V617F and special SNP and the negative regulator of JAK2-STAT pathway.
Of all 61 patients, 34 (55.7%) harbor JAK2 V617F, and the JAK2 V617F mutation was associated with leukocytosis, high hemoglobin level and increased thrombotic event significantly. We noted that special SNP was significantly associated with JAK2 V617F. The special G-allele of rs10974944 and the JAK2 V617F was highly linked. The results of Q-PCR (quantitative-polymerase chain reaction) also demonstrated significant difference between ET patients and normal individuals on SOCS and PIAS expressions.
In summary, our study showed 55.7% of ET patients had JAK2 V617F and the mutation was associated with clinical presentations. The special SNP near JAK2 was also associated with the mutation, which might provide genetic mutation benefit or survival benefit of blood cells for progression of the disease. The regulatory mechanism also takes part in the pathomechanism of the development of ET. These results will help the understanding of ET for further investigations.

並列關鍵字

JAK2 ； essential thrombocythemia ； single nucleotide polymorphism

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